UNS: Nanotopographical Memory Modulates Stem Cell Fate

West Virginia University Research Corporation, Morgantown WV

Investigators

Abstract

1511759 Yang, Yong Conventional cell culture methods using flat, stiff plastic surfaces do not recapitulate characteristics (e.g., stiffness and nanotopography) of the extracellular matrix (ECM) with which cells interact in vivo. Therefore, cell behavior on such surfaces significantly deviate from their in vivo counterparts. There is a pressing need to incorporate the ECM characteristics into stem cell culture technologies. The goal of this research is to advance next-generation cell culture technologies by investigating nanotopographical memory effects of stem cells. ECM/substrate nanotopography and stiffness critically influence numerous developmental, physiological and pathological processes in vivo, and have a profound influence on cell behavior and stem cell fate decision in vitro. It is hypothesized that stem cells can retain nanotopographical information from past culture environments and the nanotopographical memory can influence future fate decision of stem cells. The objective of the proposed research is to test this hypothesis and to delineate the underlying mechanism of nanotopographical memory effects. Three research objectives using human mesenchymal stem cells (hMSCs) as model cells are proposed to study the nanotopographical memory effects: (1) Regulate Yes-associated protein (YAP) intracellular localization by using nanotopography, (2) Validate nanotopographical memory effects, and (3) Delineate the underlying mechanism of nanotopographical memory effects. This research will advance the understanding of cellular mechanotransduction and stem cell plasticity during developmental and pathological processes. It will call attention to unintended nanotopographical memory effects during in vitro culture, which may affect stem cell function and differentiation. This research will contribute to the development of next-generation stem cell culture technologies, and provide insight into the design of new biomaterials and the cell-substrate interfaces of implants and medical devices for regenerative medicine. In addition, a collaborative, cross-disciplinary, learn-through-research system will be established to provide the basic infrastructure to promote nanobiotechnology education in West Virginia. This award by the Biotechnology and Biochemical Engineering Program of CBET is co-funded by the Biomaterials Program of the Division of Materials Research.